Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In SK-N-MC human neuroblastoma cells, the cAMP response to 10 nM isoproterenol (ISO) is mediated primarily by beta 1-adrenergic receptors. However, responses to higher concentrations of ISO (100-1000 nM) were only weakly blocked by beta 1- and beta 2-selective antagonists. When beta 1 receptors were blocked with 10 microM CGP 20712A, catecholamines still maximally activated cAMP accumulation, with only small decreases in potency. In the presence of CGP 20712A, beta blockers inhibited the response to ISO stereoselectively but with relatively low potencies. Pindolol derivatives were partial agonists with low potencies, and the atypical agonist BRL 37344 was a partial agonist with an intermediate potency. All binding sites in these cells labeled by 125I-cyanopindolol were of the beta 1 subtype. Nuclease protection assays indicated that SK-N-MC cells contain mRNA for both the human beta 1- and beta 3-adrenergic receptors, with the beta 3 subtype mRNA being expressed 25-50% more abundantly than that for the beta 1 subtype. Northern blot hybridizations showed the presence of two beta 3 mRNA transcripts of 3.1 and 2.4 kilobases. These results suggest that beta 1- and atypical beta-adrenergic receptors coexist in these cells and cause redundant increases in cAMP formation. Although molecular approaches suggest that the atypical subtype is the beta 3, the observed drug specificity differs from that reported for the expressed recombinant human beta 3 receptor.
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PMID:Coexisting beta 1- and atypical beta-adrenergic receptors cause redundant increases in cyclic AMP in human neuroblastoma cells. 135 96

We propose that leukocyte-derived cytokines induce the expression of adhesion molecules on the surface of neural cells that facilitates the subsequent attachment of leukocytes. Leukocyte adherence may contribute to some of the neural cell injury seen with various inflammatory diseases of the nervous system. With an in vitro model system, we have shown that mononuclear leukocytes bind to human neuroblastoma and cortical neuron cells only after the neural cells are stimulated with TNF-alpha. TNF-alpha stimulates expression of vascular cell adhesion molecule-1 (VCAM-1) in both of these neural cell lines. VCAM-1 mRNA is increased and VCAM-1 protein can be identified on the neural cell membranes with a new VCAM-1-specific mAb, CL40/2 F8. TNF-alpha also induces ICAM-1 in both of these neural cell lines. Leukocyte beta 1 (CD29) and beta 2 (CD18) integrins and their respective ligands, ICAM-1 and VCAM-1, on neural cells appear to be the dominant ligands mediating MNL:neural cell adhesive interactions. mAb to CD18 block 32 to 57% of the MNL binding to neural cells; similar inhibition is seen with mAb to ICAM-1. mAb to CD29 block 16 to 17% of the MNL binding to the neural cells suggesting that leukocyte beta 1 integrins and neural VCAM-1 may be a second route for MNL:neural cell interactions. Addition of both anti-CD18 and anti-CD29 mAb have an additive blocking effect; both ligand pairs may participate in MNL adhesion to neural cells, reminiscent of the multiplicity of ligands used by MNL when binding to endothelium.
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PMID:Induction of VCAM-1 and ICAM-1 on human neural cells and mechanisms of mononuclear leukocyte adherence. 137 96

Cultured human neuroblastoma cells can be classified morphologically into 3 types: neuroblastic (N), intermediate (I) and substrate adherent (S). Neuroblastoma cells of all types were found to attach and display distinct morphological characteristics on fibronectin, with S-type cells attaching better than N-type cells. Studies of the expression of integrin fibronectin receptors (alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1 and alpha V beta 1) were carried out using a total of 26 morphologically distinct cell lines and their subpopulations. Fluorescence-activated cell sorting (FACS) analysis and immunoprecipitation revealed that all S-type cells expressed abundant alpha 5 beta 1, while N-type cells barely expressed this molecule. Although alpha 3 beta 1 expression of S-type cells was also higher than that of N-type cells, some N-type cells had significantly increased levels of this molecule. alpha 4 beta 1 was found to be randomly expressed. All cell lines tested expressed alpha V beta 1. Human neuroblastoma cells, the majority of which are N-type cells with very low alpha 5 beta 1 expression, are also contrasted with other childhood cancer cells (rhabdomyosarcoma, Ewing's sarcoma, and glioma), all of which expressed high levels of alpha 5 beta 1. The characteristic expression of integrin fibronectin receptors may account for the clinically unique tumor behavior, and the immunohistochemical staining for integrins may become a useful alternative to conventional histology in differential diagnosis and a marker for prognosis in neuroblastoma.
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PMID:Unique expression of integrin fibronectin receptors in human neuroblastoma cell lines. 153 85

Human neural-crest-derived tumor cell lines, including three neuroblastomas, an astrocytoma, a glioblastoma, a rhabdomyosarcoma and a melanoma were screened for the expression of the integrin alpha 4 beta 1 (VLA-4). The neuroblastomas IMR-32 and SK-N-SH, the astrocytoma 131-INI, the glioblastoma Fogerty and the rhabdomyosarcoma TE-671 expressed alpha 4 beta 1 as determined by cytofluorometry and immunoprecipitation. Another neuroblastoma line, LA-N-1, did not express alpha 4 beta 1. Analysis of immunoprecipitated alpha 4 beta 1 showed that the alpha 4 subunit from the various cell types differed in relative molecular weight (M(r)). The variability in the observed M(r) could be accounted for by differences in the levels of N-linked glycosylation. The observed variability in M(r) did not appear to affect function since intact cells and solubilized alpha 4 beta 1 bound to a synthetic peptide identical in sequence to the CS-1 region of the alternatively spliced IIICS domain of fibronectin, a known alpha 4 beta 1 ligand.
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PMID:Expression and ligand-binding function of the integrin alpha 4 beta 1 (VLA-4) on neural-crest-derived tumor cell lines. 153 75

We have found a substantial decrease in the level of Na,K-ATPase beta 2-subunit mRNA in xenografts of human renal, lung hepatocellular carcinomas in nude mice as compared with corresponding normal tissues, as well as in the neuroblastoma cell line as compared with the neuron primary cell culture. The level of beta 1 mRNA is decreased in kidney and lung tumor cells, but is unchanged in hepatocellular carcinoma. In the neuroblastoma cell line the level of beta 1 subunit mRNA was found to be higher then in neuron primary cell culture. The level of alpha 1 mRNA in investigated tumors was the same as in normal tissues. These results may give evidence of the involvement of beta 2-subunit in the process of tumorigenesis as was shown for some other adhesion molecules.
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PMID:Tissue-specific expression of Na,K-ATPase beta-subunit. Does beta 2 expression correlate with tumorigenesis? 165 77

Monoclonal antibodies (mAbs) recognizing the disialoganglioside II3(NeuAc)2GgOse3Cer (GD2) were produced by immunizing mice with the GD2-expressing neuroblastoma cell line LAN-1 and a prefusion boost with purified GD2 coupled to Salmonella minnesota. Two IgM mAbs were isolated which demonstrated high levels of reactivity (binding ratios in excess of 100) with GD2 by solid-phase radioimmunoassay and positivity in high-performance thin-layer chromatography (HPTLC) immunostain; only one (DMAb-20) was subsequently shown by analysis with a panel of defined ganglioside species to be specific for the minimum epitope of GD2 GalNAc beta 1-4(NeuAc alpha 2-8-NeuAc alpha 2-3)Gal-, DMAb-20 was used to evaluate the expression of GD2 by malignant glioma and medulloblastoma cell lines using cell surface radioimmunoassay. indirect membrane immunofluorescence. HPTLC immunostain, and densitometric analysis of extracted gangliosides from selected cell lines. Sixteen of 20 (80%) malignant glioma and 5 of 5 medulloblastoma cell lines reacted with DMAb-20; in agreement with previous studies, 5 of 5 neuroblastoma and 2 of 3 melanoma cell lines also reacted with DMAb-20, GD2 was proportionally increased in the glioma and medulloblastoma cell lines relative to levels in normal brain, as determined by densitometric analysis. In a phenotypic survey of malignant glioma biopsies, tumor cells in 24 of 30 (80%) cases stained positively with DMAb-20. Reactive astrocytes, both within the adjacent to tumors, were frequently intensely stained. Among the morphological variants of glioblastoma examined, the most intense staining with DMAb-20 was observed in neoplastic gemistocytes, with the weakest or absent staining in small cell glioblastomas. As GD2 is a commonly expressed surface antigen of gliomas and medulloblastomas, expression of which is retained in tissue culture. DMAb-20 will be useful in determining the functional role of GD2 in cell-cell interaction, adhesion, and invasion, and in defining altered growth control mechanisms of central nervous system neoplasms in in vitro models.
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PMID:Disialoganglioside GD2 in human neuroectodermal tumor cell lines and gliomas. 165 6

Neuroblastoma cells are frequently used as targets in studies of autoimmune diseases of the nervous system. We examined the human neuroblastoma cell line, LAN-5, for the presence of autoantigens that react with naturally occurring autoantibodies in human sera. Antibodies to the HNK-1 and Gal(beta 1-3)GalNAc epitopes, which have been implicated in human autoimmune neuropathy and motor neuron disease, respectively, immunostained the surface of the neuroblastoma cells, and antibodies to the 200 kDa high molecular weight neurofilament protein (NFH) immunostained the cytoplasm and cell processes. The NHK-1 and Gal(beta 1-3)GalNAc epitopes were associated with several glycoprotein bands in Western blots of the neuroblastoma cells, and the HNK-1 epitope was also shared by a glycolipid which co-migrated with 3-sulfoglucuronyl paragloboside (SGPG) from peripheral nerve, indicating that SGPG is synthesized in neuronal cells. Northern blot analysis revealed a single RNA band of 4800 bp for NFH in normal brain but two RNA species of 4800 and 3800 bp in both neuroblastoma and adrenal cells, confirming their common origin. The neuroblastoma cells appear to contain antigens that bind to naturally occurring autoantibodies in human serum and might therefore be useful for detecting and investigating the effects of anti-neuronal antibodies. The antibody populations being investigated, however, should be distinguished from other autoantibodies which might be present in the patients' serum.
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PMID:Autoantigens in human neuroblastoma cells. 168 43

We report the isolation from two human neuroblastoma cell lines of an Arg-Gly-Asp-dependent integrin complex capable of binding to vitronectin, fibronectin, and type I collagen. The two neuroblastoma cell lines, SK-N-SH and IMR-32, exhibit specific attachment to fibronectin and type I collagen. SK-N-SH cells exhibit a much stronger attachment to vitronectin than the IMR-32 cells, which attach poorly to this substrate. Affinity chromatography of octylglucoside extracts of 125I surface-labeled cells on GRGDSPK-Sepharose columns resulted in the specific binding and elution with GRGDSP of three radiolabeled polypeptides with relative molecular masses of 135, 115, and 90 kD when analyzed by SDS-PAGE under nonreducing conditions. In the SK-N-SH cells the 135- and 90-kD polypeptides were more abundant whereas in the IMR-32 cells the 135- and 115-kD polypeptides were more highly expressed. Liposomes prepared from fractions containing all three polypeptides bound to vitronectin, fibronectin, and type I collagen, whereas liposomes prepared from the 135- and 115-kD polypeptides bound only to fibronectin and type I collagen. Polyclonal antibodies against the alpha/beta complexes of both the vitronectin receptor and the fibronectin receptor immunoprecipitated all three polypeptides. A monoclonal antibody against beta 1 immunoprecipitated only the 135- and the 115-kD polypeptides, whereas a monoclonal antibody against beta 3 subunit immunoprecipitated the 135- and 90-kD polypeptides. Although, the 115-kD polypeptide could be recognized by an anti-beta 1 antibody, a comparison of peptide maps generated by V8 protease digestion of the 115-kD polypeptide and beta 1 subunit immunoprecipitated from GRGDSPK-Sepharose flow-through material indicated that these two polypeptides are distinct. Depletion of the 90-kD polypeptide with an anti-beta 3 monoclonal antibody did not effect the ability of the 115- and 135-kD polypeptides to bind to GRGDSPK-Sepharose. These data indicate that the SK-N-SH and IMR-32 neuroblastoma cells express a novel "beta 1-like" integrin subunit that can associate with alpha v and can bind to RGD. We propose to name this beta 1-like subunit beta n. The data reported here thus demonstrate that in these two cell lines alpha v associates with two beta subunits, beta n and beta 3, forming two heterodimers. The alpha v beta n complex mediates binding to fibronectin and type I collagen, whereas the alpha v beta 3 complex mediates binding to vitronectin.
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PMID:Isolation of a novel integrin receptor mediating Arg-Gly-Asp-directed cell adhesion to fibronectin and type I collagen from human neuroblastoma cells. Association of a novel beta 1-related subunit with alpha v. 169 26

We investigated the adhesion of three morphologically distinct human neuroblastoma cell lines (NCG, GOTO and SK-N-DZ) to intact fibronectin, central cell binding domain fragment (CBF) and CS peptide-IgG conjugates in the fibronectin molecule. Each cell line was found to express different integrin fibronectin receptors (alpha 3 beta 1, alpha 4 beta 1 and alpha 5 beta 1), although similarly attached on intact fibronectin. To CBF, NCG attached well, while GOTO moderately and SK-N-DZ poorly attached. Only GOTO adhered to CS1-IgG. RGDS inhibited the spreading of NCG and SK-N-DZ on intact fibronectin, but it barely inhibited that of GOTO. The analysis by fluorescence-activated cell sorting (FACS) revealed that NCG expressed abundant alpha 3 beta 1 and alpha 5 beta 1, but little alpha 4 beta 1, while GOTO expressed a large amount of alpha 4 beta 1 as well as alpha 5 beta 1. SK-N-DZ was undetectable in any of these molecules, but expressed alpha v beta 1, which was identified by immunoprecipitation and immunoblotting. Polyclonal antibody to alpha v beta 3 inhibited the adhesion of SK-N-DZ but not that of NCG or GOTO on intact fibronectin. These results suggest the existence of a distinct mechanism of cell adhesion to fibronectin among human neuroblastoma cell lines. It remains to be determined if such heterogeneous adhesion properties are related to the unique metastatic character of human neuroblastoma.
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PMID:Distinct mechanism of human neuroblastoma cell adhesion to fibronectin. 183 Oct 74

Retinoic acid (RA) is known to induce differentiation of neuroblastoma cells in vitro. Here we show that treatment of two human neuroblastoma cell lines, SY5Y and IMR32, with RA resulted in a fivefold increase of the integrin alpha 1/beta 1 expression. The effect was selective because expression of the alpha 3/beta 1 integrin, also present in these cells, was not increased. The up-regulation of the alpha 1/beta 1 differentiated SY5Y cells correlated with increased neurite response to laminin. In fact, RA-treated SY5Y cells elongated neurites on laminin-coated substratum more efficiently compared with untreated cells or cells treated with nerve growth factor, insulin, or phorbol 12-myristate 13-acetate. These three agents induced partial morphological differentiation but did not increase alpha 1 integrin expression. Neurite extension in RA-treated cells was more efficient on laminin than on fibronectin or collagen type I and was inhibited with beta 1 integrin antibodies on all three substrates. Affinity chromatography experiments showed that alpha 1/beta 1 is the major laminin receptor in both untreated and RA-treated SY5Y cells. These data show that RA, a naturally occurring morphogen implicated in embryonic development, can selectively regulate the expression of integrin complexes in neuronal cells and suggest an important role of the alpha 1/beta 1 laminin receptor in the morphological differentiation of nerve cells.
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PMID:Up-regulation of the integrin alpha 1/beta 1 in human neuroblastoma cells differentiated by retinoic acid: correlation with increased neurite outgrowth response to laminin. 183 59


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